Methods and systems for preparing compositions

ABSTRACT

Embodiments described herein generally relate to methods and systems for preparing compositions, such as those comprising hydrogen gas. In some embodiments, the method comprises injecting liquid hydrogen and/or a liquid noble gas(es) into another liquid (e.g., a composition) such that at least a portion of the liquid hydrogen and/or liquid noble gas(es) can change phase into a gaseous phase. The liquid noble gas may be, for example, liquid xenon, liquid argon, or the like. In some embodiments, the gaseous hydrogen and/or the liquid noble gas(es) may infuse with the composition (e.g., such that at least a portion of the hydrogen gas and/or noble gas(es) is dissolved within the composition). Such compositions comprising hydrogen gas and/or noble gas(es) may be useful, for example, for the treatment of animal and human diseases, for improvement in athletic performance, for the enhancement of the overall health of a subject, or the like. Such compositions and/or liquids described herein may be administered (e.g., orally) to a subject, e.g., drunk by a subject.

FIELD OF THE INVENTION

The present invention generally relates to methods and systems forpreparing compositions, such as those comprising hydrogen and/or othergases.

BACKGROUND

H₂ has been shown to have positive effects on animal and humanphysiology and disease states. H₂ can be administered to a subject inthe form of, for example, a gas, an infusion, a topical solution, orthrough the drinking of H₂-enriched water. Production of hydrogen-richwater has been accomplished by several methods, ranging fromlarge-scale, but less self-stable, manufacturing techniques tosmall-volume single use devices for locally generating hydrogen gas.However, improved techniques for producing hydrogen-rich water or otherliquids are still needed.

SUMMARY OF THE INVENTION

The present invention provides methods and systems for preparingcompositions, such as those comprising hydrogen and/or other gases. Thesubject matter of the present invention involves, in some cases,interrelated products, alternative solutions to a particular problem,and/or a plurality of different uses of one or more systems and/orarticles.

In one aspect, methods are provided. In some embodiments, the methodcomprises introducing, into a composition, greater than or equal to 0.1mg of liquid hydrogen and administering the composition comprising theliquid hydrogen to a subject.

In some embodiments, the method comprises providing, to a subject, asealed container containing a composition pressurized using liquidhydrogen.

In some embodiments, the method comprises introducing, into a containercomprising a composition, greater than or equal to 0.1 mg of liquidhydrogen and sealing the container.

In another aspect, articles are provided. In some embodiments, thearticle comprises a sealed container containing a compositionpressurized using liquid hydrogen.

In yet another aspect, systems are provided. In some embodiments, thesystem comprises a source comprising liquid hydrogen and a dispenser influid communication with the source, the dispenser configured andarranged to introduce greater than or equal to 0.1 mg of liquid hydrogeninto containers associated with the dispenser at a rate of 100containers per minute.

In another aspect, ingestible compositions are provided. In someembodiments, the ingestible composition comprises greater than or equalto 0.1 mg and less than or equal to 5 mg liquid hydrogen and greaterthan or equal to 90 wt % an ingestible composition.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic drawing illustrating an article comprising aliquid disposed within a container, according to one set of embodiments;

FIG. 2A shows a schematic cross-sectional drawing illustrating a systemcomprising a source of liquid hydrogen, according to one set ofembodiments;

FIG. 2B shows a schematic cross-sectional drawing illustrating a systemcomprising a source of liquid hydrogen, according to one set ofembodiments;

FIG. 3 shows a schematic cross-sectional drawing illustrating a systemcomprising a dispenser, according to one set of embodiments.

Other aspects, embodiments and features of the invention will becomeapparent from the following detailed description when considered inconjunction with the accompanying drawings. The accompanying figures areschematic and are not intended to be drawn to scale. For purposes ofclarity, not every component is labeled in every figure, nor is everycomponent of each embodiment of the invention shown where illustrationis not necessary to allow those of ordinary skill in the art tounderstand the invention. All patent applications and patentsincorporated herein by reference are incorporated by reference in theirentirety. In case of conflict, the present specification, includingdefinitions, will control.

DETAILED DESCRIPTION

Embodiments described herein generally relate to methods and systems forpreparing compositions (e.g., ingestible compositions such as foodand/or drinks; physiological compositions such as blood and plasma;medicinal compositions such as medicine and/or intravenous solutions;topical compositions such as (skin) creams and/or topical ointments),such as those comprising hydrogen gas. In some embodiments, the methodcomprises introducing liquid hydrogen and/or a liquid noble gas(es) intoanother liquid (e.g., a composition) such that at least a portion of theliquid hydrogen and/or liquid noble gas(es) can change phase into agaseous phase. The liquid noble gas may be, for example, liquid xenon,liquid argon, or the like. In some embodiments, the gaseous hydrogenand/or the liquid noble gas(es) may infuse with the composition (e.g.,such that at least a portion of the hydrogen gas and/or noble gas(es) isdissolved within the composition). Such compositions comprising hydrogengas and/or noble gas(es) may be useful, for example, for the treatmentof animal and human diseases, for improvement in athletic performance,for the enhancement of the overall health of a subject, or the like.Such compositions and/or liquids described herein may be administered(e.g., orally) to a subject, e.g., drunk by a subject.

Some embodiments relate to introducing liquid hydrogen (H₂) and/or aliquid noble gas(es) into a composition and/or a container comprising acomposition, and optionally sealing the container. The liquid hydrogenand/or other gases may be kept liquid by keeping them at relatively coldtemperatures, e.g., at temperatures below their respective boilingpoints. In certain embodiments, after introduction into a container, theliquid hydrogen and/or liquid noble gas(es) change phase into gaseousphase, such that the contents (e.g., the composition, hydrogen gas,liquid noble gas(es), and/or any additives) contained within the sealedcontainer are pressurized, e.g., as one or more of the liquids becomegaseous or warms to a temperature greater than their respective boilingpoints. Advantageously, such containers described herein may provideliquids containing hydrogen gas and a noble gas that are shelf-stable(e.g., maintain a relatively stable concentration of hydrogen gas and/ornoble gas(es)) for relatively long periods of time (e.g., at least 7days). In some cases, such gases may be at equilibrium with beingdissolved in the liquid phase.

In certain embodiments, upon introduction of the liquid hydrogen and/orliquid noble gas(es) into a composition and/or a container comprisingthe composition, the composition comprising liquid hydrogen and/orliquid noble gas(es) may be administered (e.g., orally such as bydrinking the composition) to a subject. In some cases, the subject mayself-administer the composition (e.g., the subject drinks thecomposition from a container, such as a can).

In some cases, the system comprises a valve and/or other components(e.g., pipes, pressure gauges) configured and designed for theintroduction of liquid hydrogen and/or liquid noble gas(es) into acomposition, e.g., within a container or other article. Such valvesand/or other components, in some cases, may be designed to flow and/ordispense particularly cold liquids (e.g., liquid hydrogen) such that theliquid does not substantially change phase (e.g., until exiting, forexample, into a container comprising a composition). In someembodiments, the liquid hydrogen and/or liquid noble gas(es) is flowedthrough the system comprising a valve (e.g., a valve in fluidiccommunication with a source for the liquid hydrogen and/or liquid noblegas(es)) configured and designed for the introduction of cryogenicliquids such as liquid hydrogen and/or liquid noble gas(es).

In one set of embodiments, the system may include a system for removinggaseous hydrogen. For example, in certain embodiments, the systemcomprises a source of inert gas (for example, air, nitrogen, carbondioxide, etc.). The source of inert gas may be, for example, a gascylinder, a pressure tank, an HVAC system, or the like. In some cases,the system may be configured such that the inert gas is introducedproximate the valve and/or other components, e.g., to displace or dilutegaseous hydrogen from around the system. In some cases, the inert gasmay be blown (e.g., by a fan) or otherwise provided proximate the valveand/or other components such that e.g., the presence of gaseoushydrogen, if present, outside of the valve and/or other components maybe mitigated. In some cases, the inert gas may not be directed at aspecific location (e.g., via a pipe, duct, tube, etc.), but simplyallowed to vent around at least a portion of the system to displace anygaseous hydrogen that may be present. In other cases, however, the gasmay be directed to a specific location within the system, for example,at a valve and/or other component, using one or more pipes, ducts,tubes, etc.

As another example, a fan, a ventilation system, a blower, or the likemay be used to remove the gaseous hydrogen. Without wishing to be boundby theory, unlike inert gases such as nitrogen, hydrogen may present arisk of ignition and/or explosion if unmitigated and, as such, thesafety considerations for dispensing liquid hydrogen (e.g., which mayboil and/or evaporate under ambient conditions producing gaseoushydrogen) are substantially different than those for dispensing liquidnitrogen. Advantageously, the removal of gaseous hydrogen, for example,with the introduction of inert gas and/or air, may reduce or eliminatethe risk of ignition and/or explosion of relatively explosive gases suchas gaseous hydrogen that may, in some cases, inadvertently leak from thesystem, e.g., from the valve and/or other components. In one set ofembodiments, the system comprises one, two, or more storage containersfor containing one or more liquids (e.g., at cryogenic temperatures,such as the temperatures disclosed herein. In some cases, for example,the temperature within a storage container may be less than 300 K, lessthan 290 K, less than 280 K, less than 270 K, less than 260 K, less than250 K, less than 240 K, less than 230 K, less than 220 K, less than 210K, less than 200 K, less than 190 K, less than 180 K, less than 170 K,less than 160 K, less than 150 K, less than 140 K, less than 130 K, lessthan 120 K, less than 110 K, less than 100 K, less than 90 K, less than80 K, less than 77 K, less than 75 K, less than 70 K, less than 65 K,less than 60 K, less than 55 K, less than 50 K, less than 45 K, lessthan 40 K, less than 35 K, less than 30 K, less than 25 K, less than 20K, or less than 10 K. The storage container may be unpressurized (e.g.,at atmospheric pressure, 1 atm), or may have a pressure than is greateror less than atmospheric pressure. In some embodiments, the pressure maybe less than 10 MPa, less than 9 MPa, less than 8 MPa, less than 7 MPa,less than 6 MPa, less than 5 MPa, less than 4 MPa, less than 3 MPa, lessthan 2 MPa, less than 1 MPa, less than 900 kPa, less than 800 kPa, lessthan 700 kPa, less than 600 kPa, less than 500 kPa, less than 400 kPa,less than 300 kPa, or less than 200 kPa. In addition, in some cases, thepressure may also be greater than atmospheric pressure, or greater than100 kPa, greater than 200 kPa, greater than 300 kPa, greater than 400kPa, greater than 500 kPa, greater than 600 kPa, greater than 700 kPa,greater than 800 kPa, greater than 900 kPa, greater than 1 MPa, greaterthan 2 MPa, greater than 3 MPa, greater than 4 MPa, greater than 5 MPa,greater than 6 MPa, greater than 7 MPa, greater than 8 MPa, greater than9 MPa, greater than 10 MPa, etc. Combinations of any of these arepossible, e.g., a container may have a pressure between 300 kPa and 1MPa. Other pressures are also possible. In addition, if more than onestorage container is present, the temperature and/or pressure of thestorage containers may be the same or different.

The storage containers may, in some cases, be pressurized and/orthermally insulated containers. In some embodiments, a storage containermay formed out of a metal, such as stainless steel. The storagecontainer may also be vacuum-insulted in some cases. In some cases, thestorage container is a Dewar flask. Dewar and other vacuum-insulatedcontainers may be obtained commercially. In some cases, an inert gasand/or air may be introduced proximate the storage containers (e.g., toreduce or eliminate the risk of ignition and/or explosion by one or moreflammable gases).

One or more storage containers (e.g., sources of liquid hydrogen and/orliquid noble gas(es)) may be in fluidic communication with a valve,optionally via one or more conduits (e.g., pipes). For example, asillustrated in FIG. 2A, valve 140 is in fluidic communication withsource 130 (e.g., comprising liquid hydrogen and/or liquid noble gas(es)stored therein). In some embodiments, the valve may comprise one or morematerials suitable for controlling the flow of relatively cold liquids(e.g., a cryogenic liquid). In an exemplary embodiment, the valvecomprises austenitic stainless steel, steel alloys, carbon steel,polytetrafluoroethylene, or combinations thereof. The valve may be, forexample, a globe valve, a gate valve, a check valve, a butterfly valve,a cryogenic ball valve, or combinations thereof. The valve may dispersecryogenic liquids into a container, and in some cases, in a relativelycontrolled dose, e.g., such that the amount of liquid that flows intoeach container is substantially the same. For example, 80%, 85%, 90%, or95% of the containers may contain between 80% and 120%, between 85% and115%, between 90% and 110%, or between 95% and 105% of the averageamount of liquid deposited into the containers.

In some cases, the valve may be used to regulate the flow of liquidhydrogen and/or liquid noble gas(es) during and between introducing theliquids into one or more containers. For example, the valve may be opensuch that the liquid hydrogen and/or liquid noble gas(es) are introducedinto each container and, in some cases, the valve may be closed suchthat liquid hydrogen and/or liquid noble gas(es) is not dispensedoutside of each container (e.g., to prevent loss of liquid). One or morecontrol systems (e.g., computerized control systems) may be associatedwith the valve (e.g., to control the opening and closing of the valve).In some embodiments, the control system may be associated with the valveand configured such that valve disperses cryogenic liquids into acontainer, and in some cases, in a relatively controlled dose, e.g.,such that the amount of liquid that flows into each container issubstantially the same. In some cases, the position or degree of theopening of the valve may also be controlled, e.g., the valve may befully open, 50% open, 20% open, or fully closed, etc.

In certain embodiments, the valve comprises and/or is associated withone or more pressure regulators (e.g., to control the pressure and/orflow rate of the liquid hydrogen and/or noble gas(es) through thevalve). In some embodiments, the pressure regulator is in fluidiccommunication with the valve. In some such embodiments, the pressureregulator may be configured and designed for regulating the flow rateand/or pressure of cryogenic liquids. Such pressure regulators maycomprise austenitic stainless steel, steel alloys, carbon steel,polytetrafluoroethylene, or combinations thereof. In certainembodiments, the pressure regulator is configured such that thecryogenic liquid is introduced into one or more containers in a relativecontrolled dose (e.g., such that the amount of liquid that flows intoeach container is substantially the same) and/or at a relativelycontrolled rate (e.g., at a rate of greater than or equal to 100containers per minute).

In some cases, the valve further comprises a gas purge which allowsgases (e.g., hydrogen and/or noble gases) to escape the system. Asinsulation is generally not perfect, some amount of liquid may be heatedto form gas, e.g., within the storage containers and/or prior toreaching the valve, e.g., during flow through one or more conduits. Suchgases may be purged, e.g., via a gas purge, such that the gases are notdelivered to the containers, but instead are purged (e.g., to theatmosphere).

In one set of embodiments, the valve may comprise a heater, e.g., toremove potential blockage or “freeze-ups” of the valve. For example,water vapor (e.g., from the ambient environment) may condense on thevalves, which could lead to ice formation, blockage, or disruption ofthe flow of liquid through the valve. The heater may comprise anysuitable means for heating the valve and/or one or more conduits influidic communication with the valve. Non-limiting examples of suchheaters include, for example, heat tape (e.g., silicone-based heattape), electrical heaters, heat exchangers, heating via a suitableheating fluid (which may be a liquid or a gas, such as air). Otherheaters may also be used in other embodiments. In some cases, aninsulative material may be associated with the valve(s) and/orconduit(s) to prevent and/or reduce potential blockage or “freeze-ups.”

In addition, in some cases, the liquids flowing through the valve mayalso solidify within the valve. Accordingly, in some embodiments, aheater (and/or insulative material) may be used periodically to removeany freeze-ups, blockage, or disruption of the flow of liquid throughthe valve. The heater may be, for example, an electrical heater.

In some embodiments, the system is in fluidic communication with adispenser associated with one or more containers (e.g., such that theliquid hydrogen and/or liquid noble gas(es) may be introduced into theone or more containers). In certain embodiments, the system mayintroduce liquid hydrogen and/or liquid noble gas(es) into one or morecontainers relatively rapidly. For example, in some embodiments, thesystem may be configured to introduce liquid hydrogen and/or liquidnoble gas(es) (e.g., greater than or equal to 0.1 mg of liquid hydrogenand/or liquid noble gas(es)) into one or more containers at a rate ofgreater than or equal to 100 containers per minute, greater than orequal to 150 containers per minute, greater than or equal to 200containers per minute, greater than or equal to 250 containers perminute, greater than or equal to 300 containers per minute, greater thanor equal to 350 containers per minute, greater than or equal to 400containers per minute, greater than or equal to 450 containers perminute, greater than or equal to 500 containers per minute, greater thanor equal to 600 containers per minute, greater than or equal to 700containers per minute, greater than or equal to 800 containers perminute, greater than or equal to 900 containers per minute, or greaterthan or equal to 1000 containers per minute. In certain embodiments, thesystem may be configured to introduce liquid hydrogen and/or liquidnoble gas(es) into one or more containers at a rate of less than orequal to 1000 containers per minute, less than or equal to 900containers per minute, less than or equal to 800 containers per minute,less than or equal to 700 containers per minute, less than or equal to600 containers per minute, less than or equal to 500 containers perminute, less than or equal to 450 containers per minute, less than orequal to 400 containers per minute, less than or equal to 350 containersper minute, less than or equal to 300 containers per minute, less thanor equal to 250 containers per minute, less than or equal to 200containers per minute, or less than or equal to 150 containers perminute. Combinations of the above-referenced ranges are also possible(e.g., greater than or equal to 100 containers per minute and less thanor equal to 1000 containers per minute). Other ranges are also possible.

In certain embodiments, after dispensing of the liquid hydrogen and/orliquid noble gas(es) into one or more containers, the liquid comprisingliquid hydrogen and/or liquid noble gas(es) may be administered (e.g.,orally) to a subject (including self-administered).

The liquid hydrogen may be introduced into the container comprising thecomposition in a particular amount (e.g., such that the liquid hydrogenobtains a particular gaseous concentration upon expansion into gas phasee.g., after sealing of the container). In some embodiments, greater thanor equal to 0.1 mg, greater than or equal to 0.2 mg, greater than orequal to 0.3 mg, greater than or equal to 0.4 mg, greater than or equalto 0.5 mg, greater than or equal to 0.6 mg, greater than or equal to 0.7mg, greater than or equal to 0.8 mg, greater than or equal to 0.9 mg,greater than or equal to 1 mg, greater than or equal to 1.1 mg, greaterthan or equal to 1.2 mg, greater than or equal to 1.25 mg, greater thanor equal to 1.3 mg, greater than or equal to 1.4 mg, greater than orequal to 1.5 mg, greater than or equal to 1.6 mg, greater than or equalto 1.7 mg, greater than or equal to 1.75 mg, greater than or equal to1.8 mg, greater than or equal to 1.9 mg, greater than or equal to 2 mg,greater than or equal to 2.25 mg, greater than or equal to 2.5 mg,greater than or equal to 2.75 mg, greater than or equal to 3 mg, greaterthan or equal to 3.25 mg, greater than or equal to 3.5 mg, greater thanor equal to 3.75 mg, greater than or equal to 4 mg, greater than orequal to 4.25 mg, greater than or equal to 4.5 mg, or greater than orequal to 4.75 mg of liquid hydrogen is added per liter of composition inthe container. Without wishing to be bound by theory, 1 mg of liquidhydrogen generally corresponds to a volume of approximately 14microliters based upon a density of 70.8 mg/mL of liquid hydrogen. Incertain embodiments, the liquid hydrogen is added to the composition inan amount of less than or equal to 5 mg, less than or equal to 4.75 mg,less than or equal to 4.5 mg, less than or equal to 4.25 mg, less thanor equal to 4 mg, less than or equal to 3.75 mg, less than or equal to3.5 mg, less than or equal to 3.25 mg, less than or equal to 3 mg, lessthan or equal to 2.75 mg, less than or equal to 2.5 mg, less than orequal to 2.25 mg, less than or equal to 2 mg, less than or equal to 1.9mg, less than or equal to 1.8 mg, less than or equal to 1.75 mg, lessthan or equal to 1.7 mg, less than or equal to 1.6 mg, less than orequal to 1.5 mg, less than or equal to 1.4 mg, less than or equal to 1.3mg, less than or equal to 1.25 mg, less than or equal to 1.2 mg, lessthan or equal to 1.1 mg, less than or equal to 1 mg, less than or equalto 0.9 mg, less than or equal to 0.8 mg, less than or equal to 0.7 mg,less than or equal to 0.6 mg, less than or equal to 0.5 mg, less than orequal to 0.4 mg, less than or equal to 0.3 mg, or less than or equal to0.2 mg of liquid hydrogen per liter of composition in the container.Combinations of the above-referenced ranges are also possible (e.g.,greater than or equal to 0.1 mg and less than or equal to 5 mg, greaterthan or equal to 1.5 mg and less than or equal to 2 mg per liter ofcomposition in the container).

In some cases, the liquid hydrogen may be introduced into a compositionsuch that at least a portion of the liquid hydrogen (e.g., substantiallyall of the liquid hydrogen) changes phase into a gas at a particularconcentration (e.g., upon sealing of the container comprising thecomposition and expanded hydrogen gas) relative to the composition. Forexample, this may occur as the liquid hydrogen is heated upon exposureto the composition, and/or upon sealing of the container containing theliquid hydrogen and composition. In some embodiments, the concentrationof hydrogen gas present in the container (e.g., upon sealing of thecontainer) and dissolved in the composition is greater than or equal to0.1 ppm, greater than or equal to 0.2 ppm, greater than or equal to 0.3ppm, greater than or equal to 0.4 ppm, greater than or equal to 0.5 ppm,greater than or equal to 0.6 ppm, greater than or equal to 0.7 ppm,greater than or equal to 0.8 ppm, greater than or equal to 0.9 ppm,greater than or equal to 1 ppm, greater than or equal to 1.1 ppm,greater than or equal to 1.2 ppm, greater than or equal to 1.25 ppm,greater than or equal to 1.3 ppm, greater than or equal to 1.4 ppm,greater than or equal to 1.5 ppm, greater than or equal to 1.6 ppm,greater than or equal to 1.7 ppm, greater than or equal to 1.75 ppm,greater than or equal to 1.8 ppm, greater than or equal to 1.9 ppm,greater than or equal to 2 ppm, greater than or equal to 2.25 ppm,greater than or equal to 2.5 ppm, greater than or equal to 2.75 ppm,greater than or equal to 3 ppm, greater than or equal to 3.25 ppm,greater than or equal to 3.5 ppm, greater than or equal to 3.75 ppm,greater than or equal to 4 ppm, greater than or equal to 4.25 ppm,greater than or equal to 4.5 ppm, or greater than or equal to 4.75 ppm.In certain embodiments, the hydrogen gas is present in the compositionin an amount of less than or equal to 5 ppm, less than or equal to 4.75ppm, less than or equal to 4.5 ppm, less than or equal to 4.25 ppm, lessthan or equal to 4 ppm, less than or equal to 3.75 ppm, less than orequal to 3.5 ppm, less than or equal to 3.25 ppm, less than or equal to3 ppm, less than or equal to 2.75 ppm, less than or equal to 2.5 ppm,less than or equal to 2.25 ppm, less than or equal to 2 ppm, less thanor equal to 1.9 ppm, less than or equal to 1.8 ppm, less than or equalto 1.75 ppm, less than or equal to 1.7 ppm, less than or equal to 1.6ppm, less than or equal to 1.5 ppm, less than or equal to 1.4 ppm, lessthan or equal to 1.3 ppm, less than or equal to 1.25 ppm, less than orequal to 1.2 ppm, less than or equal to 1.1 ppm, less than or equal to 1ppm, less than or equal to 0.9 ppm, less than or equal to 0.8 ppm, lessthan or equal to 0.7 ppm, less than or equal to 0.6 ppm, less than orequal to 0.5 ppm, less than or equal to 0.4 ppm, less than or equal to0.3 ppm, or less than or equal to 0.2 ppm. Combinations of theabove-referenced ranges are also possible (e.g., greater than or equalto 0.1 ppm and less than or equal to 5 ppm, greater than or equal to 1.5ppm and less than or equal to 2 ppm). Other ranges are also possible. Inaddition, in some embodiments, no liquid hydrogen may be present.

Liquid hydrogen has a boiling point of 20 K (−253° C.) at 1 bar. Higherpressures may cause the boiling point of hydrogen to increase. Thus,liquid hydrogen at various pressures, may have a boiling point of lessthan 25 K, less than 30 K, or less than 33 K (e.g., at 1.29 MPa, thecritical point of hydrogen). Thus, the liquid hydrogen in certainembodiments may be kept at a temperature less than its boiling point(e.g., at a suitable pressure). In addition, in some cases, the liquidhydrogen may be present in supercritical state, e.g., during storageand/or upon introduction to a container or a composition. It should thusbe understood that “liquid hydrogen,” as used herein, includes bothsubcritical hydrogen and supercritical hydrogen. In some cases, however,the liquid hydrogen is only in a supercritical state. In addition, insome cases, the liquid hydrogen is only in a subcritical state.

Non-limiting examples of suitable liquid noble gases that may beintroduced to the composition include helium, neon, argon, krypton, andxenon, as well as combinations thereof. It should be understood thatthese elements are generally referred to in the art as “noble gases,”irrespective of the state of the matter that they happen to be in, i.e.,a “noble gas” may be a solid, liquid, or gas. (At room temperature, thenoble gases are gases, but that should not be read to imply that thenoble gases cannot also achieve other states of matter, such asliquids.)

In a particular set of embodiments, the liquid noble gas is liquidxenon. In some cases, two or more liquid noble gases may be present,e.g., each independently at the concentrations below. The liquid noblegas may be introduced to the composition such that the liquid noble gaschanges phase into a gas and is substantially dissolved and/or suspendedin the composition. For example, the mole fraction solubility of xenonin water at 25° C. and 1 atm is generally 7.890×10⁻⁵. In someembodiments, the amount of noble gas dissolved in the composition isgreater than the amount of noble gas that would be dissolved in thecomposition at the mole fraction solubility of the noble gas in waterdetermined at 25° C. and 1 atm. For example, the composition may beunder a pressure greater than 1 atm and/or a temperature greater than25° C., e.g., as discussed herein, which may facilitate greater amounts.

The liquid noble gas may be introduced into the container comprising thecomposition in a particular amount (e.g., such that the liquid noble gasobtains a particular gaseous concentration upon expansion into gas phasee.g., after sealing of the container). In some embodiments, greater thanor equal to 0.1 mg, greater than or equal to 0.2 mg, greater than orequal to 0.3 mg, greater than or equal to 0.4 mg, greater than or equalto 0.5 mg, greater than or equal to 0.6 mg, greater than or equal to 0.7mg, greater than or equal to 0.8 mg, greater than or equal to 0.9 mg,greater than or equal to 1 mg, greater than or equal to 1.1 mg, greaterthan or equal to 1.2 mg, greater than or equal to 1.25 mg, greater thanor equal to 1.3 mg, greater than or equal to 1.4 mg, greater than orequal to 1.5 mg, greater than or equal to 1.6 mg, greater than or equalto 1.7 mg, greater than or equal to 1.75 mg, greater than or equal to1.8 mg, greater than or equal to 1.9 mg, greater than or equal to 2 mg,greater than or equal to 2.25 mg, greater than or equal to 2.5 mg,greater than or equal to 2.75 mg, greater than or equal to 3 mg, greaterthan or equal to 3.25 mg, greater than or equal to 3.5 mg, greater thanor equal to 3.75 mg, greater than or equal to 4 mg, greater than orequal to 4.25 mg, greater than or equal to 4.5 mg, greater than or equalto 4.75 mg, greater than or equal to 5 mg, greater than or equal to 5.5mg, greater than or equal to 6 mg, greater than or equal to 6.5 mg,greater than or equal to 7 mg, greater than or equal to 7.5 mg, greaterthan or equal to 8 mg, greater than or equal to 8.5 mg, greater than orequal to 9 mg, greater than or equal to 9.5 mg, greater than or equal to10 mg, greater than or equal to 11 mg, greater than or equal to 12 mg,greater than or equal to 13 mg, greater than or equal to 14 mg, greaterthan or equal to 15 mg, greater than or equal to 16 mg, greater than orequal to 17 mg, greater than or equal to 18 mg, or greater than or equalto 19 mg of liquid noble gas (e.g., liquid xenon) is added per liter ofcomposition in the container. Without wishing to be bound by theory, 1mg of liquid xenon generally corresponds to a volume of approximately0.32 microliters based upon a density of 3.1 mg/microliters of liquidxenon.

In certain embodiments, the liquid noble gas is added to the compositionin an amount of less than or equal to 20 mg, less than or equal to 19mg, less than or equal to 18 mg, less than or equal to 17 mg, less thanor equal to 16 mg, less than or equal to 15 mg, less than or equal to 14mg, less than or equal to 13 mg, less than or equal to 12 mg, less thanor equal to 11 mg, less than or equal to 10 mg, less than or equal to9.5 mg, less than or equal to 9 mg, less than or equal to 8.5 mg, lessthan or equal to 8 mg, less than or equal to 7.5 mg, less than or equalto 7 mg, less than or equal to 6.5 mg, less than or equal to 6 mg, lessthan or equal to 5.5 mg, less than or equal to 5 mg, less than or equalto 4.75 mg, less than or equal to 4.5 mg, less than or equal to 4.25 mg,less than or equal to 4 mg, less than or equal to 3.75 mg, less than orequal to 3.5 mg, less than or equal to 3.25 mg, less than or equal to 3mg, less than or equal to 2.75 mg, less than or equal to 2.5 mg, lessthan or equal to 2.25 mg, less than or equal to 2 mg, less than or equalto 1.9 mg, less than or equal to 1.8 mg, less than or equal to 1.75 mg,less than or equal to 1.7 mg, less than or equal to 1.6 mg, less than orequal to 1.5 mg, less than or equal to 1.4 mg, less than or equal to 1.3mg, less than or equal to 1.25 mg, less than or equal to 1.2 mg, lessthan or equal to 1.1 mg, less than or equal to 1 mg, less than or equalto 0.9 mg, less than or equal to 0.8 mg, less than or equal to 0.7 mg,less than or equal to 0.6 mg, less than or equal to 0.5 mg, less than orequal to 0.4 mg, less than or equal to 0.3 mg, or less than or equal to0.2 mg of liquid hydrogen per liter of composition in the container.Combinations of the above-referenced ranges are also possible (e.g.,greater than or equal to 1 mg and less than or equal to 20 mg, greaterthan or equal to 10 mg and less than or equal to 15 mg, greater than orequal to 0.1 mg and less than or equal to 5 mg, greater than or equal to1.5 mg and less than or equal to 2 mg per liter of composition in thecontainer).

In some cases, one or more liquid noble gases may be introduced into acomposition such that at least a portion of the liquid noble gas (e.g.,substantially all of the liquid noble gas) changes phase into a gas at aparticular concentration (e.g., upon sealing of the container comprisingthe composition and expanded noble gas) relative to the composition. Forexample, this may occur as the one or more liquid noble gases are heatedupon exposure to the composition, and/or upon sealing of the containercontaining the liquid hydrogen and composition. In some embodiments, theconcentration of noble gas present in the container (e.g., upon sealingof the container) and dissolved in the composition is greater than orequal to 1 ppm, greater than or equal to 1.25 ppm, greater than or equalto 1.5 ppm, greater than or equal to 1.75 ppm, greater than or equal to2 ppm, greater than or equal to 2.25 ppm, greater than or equal to 2.5ppm, greater than or equal to 2.75 ppm, greater than or equal to 3 ppm,greater than or equal to 3.25 ppm, greater than or equal to 3.5 ppm,greater than or equal to 3.75 ppm, greater than or equal to 4 ppm,greater than or equal to 4.25 ppm, greater than or equal to 4.5 ppm,greater than or equal to 4.75 ppm, greater than or equal to 5 ppm,greater than or equal to 5.5 ppm, greater than or equal to 6 ppm,greater than or equal to 6.5 ppm, greater than or equal to 7 ppm,greater than or equal to 7.5 ppm, greater than or equal to 8 ppm,greater than or equal to 8.5 ppm, greater than or equal to 9 ppm,greater than or equal to 9.5 ppm, greater than or equal to 10 ppm,greater than or equal to 11 ppm, greater than or equal to 12 ppm,greater than or equal to 13 ppm, greater than or equal to 14 ppm,greater than or equal to 15 ppm, greater than or equal to 16 ppm,greater than or equal to 17 ppm, greater than or equal to 18 ppm, orgreater than or equal to 19 ppm. In certain embodiments, the noble gasis present in the composition in an amount of less than or equal to 20ppm, less than or equal to 19 ppm, less than or equal to 18 ppm, lessthan or equal to 17 ppm, less than or equal to 16 ppm, less than orequal to 15 ppm, less than or equal to 14 ppm, less than or equal to 13ppm, less than or equal to 12 ppm, less than or equal to 11 ppm, lessthan or equal to 10 ppm, less than or equal to 9.5 ppm, less than orequal to 9 ppm, less than or equal to 8.5 ppm, less than or equal to 8ppm, less than or equal to 7.5 ppm, less than or equal to 7 ppm, lessthan or equal to 6.5 ppm, less than or equal to 5 ppm, less than orequal to 4.75 ppm, less than or equal to 4.5 ppm, less than or equal to4.25 ppm, less than or equal to 4 ppm, less than or equal to 3.75 ppm,less than or equal to 3.5 ppm, less than or equal to 3.25 ppm, less thanor equal to 3 ppm, less than or equal to 2.75 ppm, less than or equal to2.5 ppm, less than or equal to 2.25 ppm, less than or equal to 2 ppm,less than or equal to 1.75 ppm, less than or equal to 1.5 ppm, or lessthan or equal to 1.25 ppm. Combinations of the above-referenced rangesare also possible (e.g., greater than or equal to 1 ppm and less than orequal to 20 ppm, greater than or equal to 10 ppm and less than or equalto 15 ppm). Other ranges are also possible. The noble gas may includexenon, and/or other gases as discussed herein. In other embodiments,however, no liquid noble gases may be used.

Liquid xenon has a boiling point of 165 K (−108° C.) at 1 bar.Similarly, the boiling points of helium, neon, argon, krypton are,respectively 4 K, 25 K, 87 K, 116 K. Higher pressures may cause theboiling point of the noble gas to increase. Thus, for example, liquidxenon at various pressures may have a boiling point of less than 170 K,less than 180 K, less than 190 K, less than 200 K, less than 210 K, lessthan 210 K, less than 220 K, less than 230 K, less than 240 K, less than250 K, less than 260 K, less than 270 K, less than 280 K, or less than290 K (e.g., at 5.8 MPa, the critical point of xenon). A liquid noblegas, in certain embodiments, may be kept at a temperature less than itsboiling point (e.g., at a suitable pressure), e.g., at temperatures lessthan the above temperatures.

In addition, in some cases, the liquid noble gas may be present insupercritical state, e.g., during storage and/or upon introduction to acontainer or a composition. It should thus be understood that a “liquidnoble gas,” as used herein, includes both noble gases in the subcriticaland supercritical states. In some cases, e.g., if more than one noblegas is present, they may each be independently present in a subcriticalor supercritical state, e.g., depending on the temperature and/orpressure. In some cases, however, all of the noble gas is present onlyin a supercritical state. In addition, in some cases, all of the noblegas is present only in a subcritical state.

In some cases, the liquid hydrogen and/or liquid noble gas(es) may beintroduced into a container (e.g., an open container comprising acomposition). For example, as illustrated schematically in FIG. 1,article 100 may comprise a liquid (for example, a composition) 110disposed in container 120. In certain embodiments, the container may besealed, e.g., to the external atmosphere, e.g., containing the liquidhydrogen and/or liquid noble gases inside. For example, in certainembodiments, the container may be sealed such that the liquid and/orgases (e.g., hydrogen gas, and/or xenon gas) within the container arenot able to substantially exit the container after sealing. In someembodiments, liquid hydrogen and/or liquid noble gas(es) may beintroduced into the container (and/or added to the composition) and thecontainer is sealed such that, upon expansion and change of phase of theliquids into gases (e.g., via heating of the liquids to more ambienttemperatures), the hydrogen gas and/or noble gas increases the pressurewithin the sealed container.

In some embodiments, a system comprising a source of liquid hydrogenand/or liquid noble gas(es) may be used to introduce the liquid hydrogenand/or liquid noble gas(es) into the container (and/or a liquid disposedtherein). For example, as illustrated in FIG. 2A, system 102 comprisessource 130 (e.g., a storage container) comprising liquid hydrogen and/orliquid noble gas(es). Source 130 may be associated with one or morecontainers (e.g., container 120) to introduce liquid hydrogen and/orliquid noble gas(es) into the container(s). In some embodiments, valve140 may be in fluidic communication (e.g., via conduit 135 such as achannel or pipe) with source 130. In certain embodiments, valve 140 isconfigured and designed for controlling the flow of liquid hydrogenand/or liquid noble gas(es) (e.g., such that the liquid hydrogen and/orliquid noble gas(es) may be introduced into a composition). In somecases, a dispenser 150 may be in fluidic communication with valve 140and/or source 130. In some embodiments, dispenser 150 is configured andarranged to introduce the liquid hydrogen (e.g., greater than or equalto 0.1 mg of liquid hydrogen) and/or liquid noble gas(es) (e.g., greaterthan or equal to 0.1 mg of liquid noble gas(es)) into container 120.

In certain embodiments, dispenser 150 may be positioned proximate anopening (e.g., opening 160) of container 120 such that the liquidhydrogen and/or liquid noble gas(es) may be introduced into container120 (and/or liquid 110 disposed therein). In some cases, the dispensermay be placed in direct contact with the liquid disposed within thecontainer such that the liquid hydrogen and/or liquid noble gas(es)(e.g., from the source) may be introduced directly into the liquid. Forexample, as illustrated in FIG. 2B, dispenser 150 may be positioned tobe in direct contact with liquid 110 disposed within container 120. Insome such embodiments, liquid hydrogen (e.g., greater than or equal to0.1 mg of liquid hydrogen) and/or liquid noble gas(es) (e.g., greaterthan or equal to 0.1 mg of liquid noble gas(es)) may be introduceddirectly into liquid 110.

In some embodiments, the dispenser and valve(s) may be designed suchthat the flow rate of the liquid hydrogen and/or liquid noble gas(es)(e.g., the flow rate from the source and/or the flow rate into thecontainer) may be controlled. For example, as illustrated in FIG. 3,system 300 comprises inlet 310 (e.g., in fluidic communication with asource of liquid hydrogen and/or liquid noble gas(es)), vessel 315 influidic communication with inlet 310, and outlet 230 in fluidiccommunication with vessel 315. In certain embodiments, outlet 320 is influidic communication with dispenser 330 and associated with valve 325(e.g., for opening and closing outlet 320 such that the flow of liquidhydrogen and/or liquid noble gas(es) through dispenser 330 may becontrolled). In some embodiments, a sensor 340 (e.g., a pressure sensor,a flow sensor) may be associated with (e.g., disposed within) vessel315. Sensor 340 may be in electronic communication (e.g., via electricalconnection 342 such as a data transmission cable) with a controller 350.Controller 350 may, in some cases, be configured to control the flowrate, pressure, and/or amount of liquid hydrogen and/or liquid noblegas(es) dispensed (e.g., into a container) via system 300.

In certain embodiments, the controller may be configured to allow a userto adjust various parameters (e.g., flow rate, pressure, etc.) based onpreference.

In some embodiments, the controller may be configured to adjust variousparameters based on external metrics. For example, in certainembodiments, the controller is configured adjust the flow rate inresponse to a signal from the sensor in communication with thecontroller. Non-limiting examples of suitable sensors for use with thesystems and methods described herein include temperature sensors,environmental sensors (e.g., humidity, ambient air temperature, light,air flow), flow sensors, or the like. In some embodiments, thecontroller adjusts the flow rate of the liquid hydrogen and/or liquidnoble gas(es) in response to an input from the user and/or a signal fromthe sensor.

In some embodiments, the controller may include one or more processcontrol systems, such as proportional, integral, and/or derivative (PID)feedforward and/or feedback loops, to adjust the flow rate (e.g., inresponse to one or more sensors in communication with the controller).

The controller may be implemented by any suitable type of analog and/ordigital circuitry. For example, the controller may be implemented usinghardware or a combination of hardware and software. When implementedusing software, suitable software code can be executed on any suitableprocessor (e.g., a microprocessor) or collection of processors. The oneor more controllers can be implemented in numerous ways, such as withdedicated hardware, or with general purpose hardware (e.g., one or moreprocessors) that is programmed using microcode or software to performthe functions recited above. In this respect, it should be appreciatedthat one implementation of the embodiments described herein comprises atleast one computer-readable storage medium (e.g., RAM, ROM, EPROM, flashmemory or other memory technology, or other tangible, non-transitorycomputer-readable storage medium) encoded with a computer program (i.e.,a plurality of executable instructions) that, when executed on one ormore processors, performs the above-discussed functions of one or moreembodiments. In addition, it should be appreciated that the reference toa computer program which, when executed, performs any of theabove-discussed functions, is not limited to an application programrunning on a host computer. Rather, the terms computer program andsoftware are used herein in a generic sense to reference any type ofcomputer code (e.g., application software, firmware, microcode, or anyother form of computer instruction) that can be employed to program oneor more processors to implement aspects of the techniques discussedherein.

In some cases, the seal may be removable (e.g., such that thecomposition may be removed from the container and/or orally administeredto a subject, e.g., drunk). For example, in an exemplary embodiment, thecontainer is a can and the can may be unsealed by breaking the seal ofthe can (e.g., via a pull-tab, push-tab, or stay-tab associated with theseal). In another exemplary embodiment, the container is a bottle orpouch, and the container may be unsealed by removing a cap associatedwith an opening of the container. Upon unsealing of the container, thecomposition may be ingested (e.g., drunk) by the subject. In some cases,the container may be used for intravenous infusion, or otheradministration techniques such as those described herein.

Non-limiting examples of suitable types of containers include cans(e.g., aluminum or tin cans), bottles, jars, pouches, boxes, bags, andcapsules (e.g., a liquid gel capsule). Other containers are alsopossible and those of ordinary skill in the art would be capable ofselecting suitable containers based upon the teachings of thisspecification. The container may also comprise any suitable material.For example, in some embodiments, the container may comprise a materialsuch as metal (e.g., aluminum, tin, iron, etc.), metal alloys (e.g.,steel), polymer (e.g., polyethylene, polystyrene, polypropylene,polyether ether ketones, polyethylene terephthalate, polyvinylchloride),glass (e.g., borosilicate glass), resin, and combinations thereof. Incertain embodiments, the fluid is present in the container is at or nearatmospheric pressure. In some cases, however, the container is able tocontain an elevated pressure therein (e.g., a pressure greater thanatmospheric pressure).

In addition, in some embodiments, one or more coatings or othermaterials may be used to facilitate retention of gases within thecontainer, e.g., such materials may be relatively gas-impermeable. Avariety of gas-impermeable materials may be readily obtainedcommercially, and coated onto a surface of the container and/or embeddedwithin the materials forming the container. Non-limiting examples ofgas-impermeable materials include polyester, nylon (e.g., MXD6 nylon ornylon 6), ethylene vinyl alcohol (EVA), silicon oxides (SiO_(x)), or thelike.

In certain embodiments, the container has a volume of less than about100 mL, less than 75 mL, less than 50 mL, less than 25 mL, less than 10mL, less than 5 mL, less than 3 mL, or less than 1 mL. In some cases,the volume of liquid is at least 1 mL, at least 3 mL, at least 5 mL, atleast 10 mL, at least 25 mL, at least 50 mL, or at least 75 mL.Combinations of the above-referenced ranges are also possible (e.g.,between 75 mL and 10 mL). Other ranges are also possible.

In some embodiments, the container may have a particular volume such asa volume of greater than or equal to 100 mL (e.g., greater than or equalto 250 mL, greater than or equal to 500 mL, greater than or equal to 750mL, or greater than or equal to 1 L). In certain embodiments, thecontainer has a volume of less than or equal to 2 L (e.g., less than orequal to 1 L, less than or equal to 750 mL, less than or equal to 500mL, or less than or equal to 250 mL). Combinations of theabove-references are also possible (e.g., greater than or equal to 100mL and less than or equal to 2 L). Other ranges are also possible. Insome cases, for instance, the volume of the container may be about 150mL, about 200 mL, about 222 mL, about 237 mL, about 250 mL, about 330mL, about 341 mL, about 350 mL, about 355 mL, about 375 mL, about 440mL, about 473 mL, about 500 mL, about 568 mL, or about 1,000 mL.

In some embodiments, the container has a particular pressure that may begreater than atmospheric pressure. The pressure may be created withinthe container using any of a variety of gases, including air, nitrogen,carbon dioxide, water vapor, hydrogen gas, one or more noble gases (suchas xenon), or the like, as well as combinations of these and/or othersuitable gases. For example, liquid hydrogen and/or liquid noble gasesmay be introduced into the container (e.g., added to the compositiondisposed with the container) such that upon phase change of the liquidhydrogen and/or liquid noble gases into a gaseous phase, the pressureinside the container increases. Such gases may be at equilibrium withthe liquid within the container. In addition, in some cases, one or moreof the gases may be present in an amount such that at equilibrium, thosegases are dissolved within the liquid, for example, at saturationconcentrations.

For example, in certain embodiments, the container contains a pressure(e.g., is pressurized to a pressure of) at least 1 psi (1 psi is about6894.757 Pa), at least 2 psi, at least 3 psi, at least 5 psi, at least 7psi, at least 10 psi, at least 12 psi, at least 15 psi, at least 18 psi,at least 20 psi, at least 25 psi, at least 30 psi, at least 35 psi, atleast 40 psi, or at least 45 psi greater than atmospheric pressure. Insome embodiments, the container contains a pressure of less than orequal to 50 psi, less than or equal to 45 psi, less than or equal to 40psi, less than or equal to 35 psi, less than or equal to 30 psi, lessthan or equal to 25 psi, less than or equal to 20 psi, less than orequal to 18 psi, less than or equal to 15 psi, less than or equal to 12psi, less than or equal to 10 psi, less than or equal to 7 psi, lessthan or equal to 5 psi, less than or equal to 3 psi, or less than orequal to 2 psi greater than atmospheric pressure. Combinations of theabove-referenced ranges are also possible (e.g., at least 1 psi and lessthan or equal to 50 psi greater than atmospheric pressure). Other rangesare also possible.

Those of ordinary skill in the art would be capable of selectingsuitable amounts of liquid hydrogen and/or liquid noble gases tointroduce to the container, based upon the teachings of thisspecification, such that the container is pressurized to a pressure inone or more ranges described above.

In some embodiments, the article comprises a gaseous headspace (e.g., agaseous headspace present within the container). The gaseous headspacemay comprise a variety of gases, such as oxygen, air, noble gases, orthe like. For example, referring again to FIG. 1, in some cases, article100 comprises gaseous headspace 115. The article may comprise anysuitable amount of headspace within the container. In some embodiments,the headspace occupies greater than or equal to 0.1 vol %, greater thanor equal to 0.2 vol %, greater than or equal to 0.25 vol %, greater thanor equal to 0.5 vol %, greater than or equal to 0.75 vol %, greater thanor equal to 1 vol %, greater than or equal to 1.25 vol %, greater thanor equal to 1.5 vol %, greater than or equal to 1.75 vol %, greater thanor equal to 2 vol %, greater than or equal to 2.25 vol %, greater thanor equal to 2.5 vol %, greater than or equal to 3 vol %, greater than orequal to 3.5 vol %, greater than or equal to 4 vol %, or greater than orequal to 4.5 vol % of the volume contained by the container. In certainembodiments, the headspace occupies less than or equal to 5 vol %, lessthan or equal to 4.5 vol %, less than or equal to 4 vol %, less than orequal to 3.5 vol %, less than or equal to 3 vol %, less than or equal to2.5 vol %, less than or equal to 2.25 vol %, less than or equal to 2 vol%, less than or equal to 1.75 vol %, less than or equal to 1.5 vol %,less than or equal to 1.25 vol %, less than or equal to 1 vol %, lessthan or equal to 0.75 vol %, less than or equal to 0.5 vol %, less thanor equal to 0.25 vol %, or less than or equal to 0.2 vol % of the volumecontained by the container. Combinations of the above-referenced rangesare also possible (e.g., greater than or equal to 0.1 vol % and lessthan or equal to 5 vol %). Other ranges are also possible.

In some embodiments, the gaseous headspace comprises hydrogen gas. Incertain embodiments, the gaseous headspace comprises a noble gas such asxenon gas. In some cases, both hydrogen gas and the noble gas (e.g.,xenon gas) may be present in the headspace. As mentioned, other gases(including other noble gases) may be present as well, e.g., as discussedherein. In some embodiments, when hydrogen gas and/or a noble gas suchas xenon gas are present in the headspace, the concentration of hydrogengas and/or xenon gas greater than the concentration of the gas thatwould result from the saturation vapor pressure of the gas.

For example, in some embodiments, the headspace comprises greater thanor equal to 0.00001 vol %, greater than or equal to 0.00005 vol %,greater than or equal to 0.0001 vol %, greater than or equal to 0.0005vol %, greater than or equal to 0.001 vol %, greater than or equal to0.005 vol %, greater than or equal to 0.01 vol %, greater than or equalto 0.05 vol %, greater than or equal to 0.1 vol %, greater than or equalto 0.5 vol %, greater than or equal to 1 vol %, greater than or equal to2 vol %, greater than or equal to 5 vol %, greater than or equal to 10vol %, greater than or equal to 20 vol %, greater than or equal to 30vol %, greater than or equal to 40 vol %, greater than or equal to 50vol %, or greater than or equal to 60 vol % xenon gas (and/or othernoble gases) versus the total volume of the headspace. In certainembodiments, xenon gas (and/or other noble gases) is present in theheadspace in an amount less than or equal to 70 vol %, less than orequal to 60 vol %, less than or equal to 50 vol %, less than or equal to40 vol %, less than or equal to 30 vol %, less than or equal to 20 vol%, less than or equal to 10 vol %, less than or equal to 5 vol %, lessthan or equal to 2 vol %, less than or equal to 1 vol %, less than orequal to 0.5 vol %, less than or equal to 0.1 vol %, less than or equalto 0.05 vol %, less than or equal to 0.01 vol %, less than or equal to0.005 vol %, less than or equal to 0.001 vol %, less than or equal to0.0005 vol %, less than or equal to 0.0001 vol %, or less than or equalto 0.00005 vol % versus the total volume of the headspace. Combinationsof the above-referenced ranges are also possible (e.g., greater than orequal to 0.00001 vol % and less than or equal to 10 vol %). Other rangesare also possible.

In certain embodiments, the headspace comprises greater than or equal to0.00001 vol %, greater than or equal to 0.00005 vol %, greater than orequal to 0.0001 vol %, greater than or equal to 0.0005 vol %, greaterthan or equal to 0.001 vol %, greater than or equal to 0.005 vol %,greater than or equal to 0.01 vol %, greater than or equal to 0.05 vol%, greater than or equal to 0.1 vol %, greater than or equal to 0.5 vol%, greater than or equal to 1 vol %, greater than or equal to 2 vol %,or greater than or equal to 5 vol % hydrogen gas versus the total volumeof the headspace. In certain embodiments, hydrogen gas is present in theheadspace in an amount less than or equal to 10 vol %, less than orequal to 5 vol %, less than or equal to 2 vol %, less than or equal to 1vol %, less than or equal to 0.5 vol %, less than or equal to 0.1 vol %,less than or equal to 0.05 vol %, less than or equal to 0.01 vol %, lessthan or equal to 0.005 vol %, less than or equal to 0.001 vol %, lessthan or equal to 0.0005 vol %, less than or equal to 0.0001 vol %, orless than or equal to 0.00005 vol % versus the total volume of theheadspace. Combinations of the above-referenced ranges are also possible(e.g., greater than or equal to 0.00001 vol % and less than or equal to10 vol %). Other ranges are also possible.

In one set of embodiments, the liquid within the sealed container fillsgreater than or equal to 50 vol %, greater than or equal to 75 vol %,greater than or equal to 80 vol %, greater than or equal to 85 vol %,greater than or equal to 90 vol %, greater than or equal to 92 vol %,greater than or equal to 95 vol %, greater than or equal to 98 vol %,greater than or equal to 99 vol %, greater than or equal to 99.5 vol %,or greater than or equal to 99.9 vol % of the volume of the sealedcontainer. In some cases, the volume of the liquid may be less than orequal to 99.99 vol %, less than or equal to 99.9 vol %, less than orequal to 99.5 vol %, less than or equal to 99 vol %, less than or equalto 98 vol %, less than or equal to 95 vol %, less than or equal to 92vol %, less than or equal to 90 vol %, less than or equal to 85 vol %,less than or equal to 80 vol %, or less than or equal to 75 vol % of thevolume of the sealed container. Combinations of the above-referencedranges are also possible (e.g., greater than or equal to 50 vol % andless than or equal to 99.99 vol %).

In some embodiments, the articles (e.g., a sealed container) describedherein are configured to have a relatively long shelf life with respectto the gases contained therein. In certain embodiments, the hydrogen gasand noble gas (e.g., xenon gas) does not substantially leak from thesealed container for at least 7 days, or longer (e.g., 14 days, 28 days,56 days, etc.). For example, in some embodiments, greater than or equalto 50 vol %, greater than or equal to 75 vol %, greater than or equal to80 vol %, greater than or equal to 85 vol %, greater than or equal to 90vol %, greater than or equal to 92 vol %, greater than or equal to 95vol %, greater than or equal to 98 vol %, greater than or equal to 99vol %, greater than or equal to 99.5 vol %, or greater than or equal to99.9 vol % of the hydrogen gas and/or xenon gas (and/or other noblegases) is present in the sealed container and/or in the headspace 7 daysafter sealing of the container (including the liquid comprising thehydrogen gas and the noble gas). In certain embodiments, less than orequal to 99.99 vol %, less than or equal to 99.9 vol %, less than orequal to 99.5 vol %, less than or equal to 99 vol %, less than or equalto 98 vol %, less than or equal to 95 vol %, less than or equal to 92vol %, less than or equal to 90 vol %, less than or equal to 85 vol %,less than or equal to 80 vol %, or less than or equal to 75 vol % of thehydrogen gas and/or xenon gas (and/or other noble gases) is present inthe sealed container and/or in the headspace 7 days after sealing of thecontainer (including within the composition comprising the hydrogen gasand the noble gas). Combinations of the above-referenced ranges are alsopossible (e.g., greater than or equal to 50 vol % and less than or equalto 99.99 vol %). Other ranges are also possible.

In some embodiments, the composition comprising hydrogen and/or noblegases is an ingestible composition. One of ordinary skill in the artwould understand that the term “ingestible” as used herein is notintended to encompass any and all substances and/or compositions thatmay be placed in a subject's body (e.g., via swallowing or drinking).Ingestible compositions are those that are edible, e.g., typicallyintended to be digested and absorbed by the body of the subject fore.g., nourishment, pleasure, therapeutic effect, and/or energy. In someembodiments, the ingestible composition is non-toxic, although those ofordinary skill in the art would understand that some ingestiblecompositions, such as therapeutic agents, may have some negligible levelof toxicity but which provide a therapeutic benefit. By way of example,a stainless steel ball, while a capable of being swallowed by a subject,would not be considered an ingestible composition as e.g., it providesno nourishing, pleasure, or therapeutic effect on the subject.Similarly, antifreeze, while a liquid, would not be considered aningestible composition (e.g., as it provides a detrimental effect on thebody of the subject). By contrast, and by way of example without wishingto be limited by such, a liquid such as water or food such as pudding,which are generally consumed for nourishment and/or pleasure, would eachbe considered an ingestible composition.

The composition comprising hydrogen and/or noble gases may be, forexample, an ingestible composition including a liquid such as water (orother drinkable liquids), optionally with a variety of additives, suchas sugar, electrolytes, caffeine, salt(s), flavoring, vitamins, herbs,amino acids, tea extracts, seed extracts, fruit extracts. The liquid maybe any of a variety of drinkable liquids, such as a fruit juice or ajuice-like beverage (e.g., powdered drinks such as Crystal Light®,Kool-Aid®, or the like), coffee, tea, a sports drink, an energy drink,soda pop, milk (e.g., cow's milk, goat's milk, sheep's milk, low-fatmilk, whole milk, cream, chocolate milk), an alcoholic drink (e.g.,mixed alcoholic beverages, wine, beer), or the like.

In some cases, the composition (e.g., an ingestible composition)comprises a food. For example, the composition may include a food suchas frozen foods including but not limited to, for example, ice cream,sorbet, gelato, or the like. In some cases, the composition may includea food such as an ingestible colloid, gel, and/or suspension includingbut not limited to, for example, puddings, custards, and Jell-O®. In anillustrative embodiment, hydrogen gas and/or noble gas(es) may be addedto a composition such as a food which does not require further heatingprior to ingestion (e.g., refrigerated prepared foods, liquids,colloids, gels, and/or suspensions) such that, for example, the hydrogengas and/or noble gas(es) are not boiled out of the composition.

In certain embodiments, the composition (e.g., comprising hydrogenand/or noble gas(es)) may be configured to be administered (e.g.,orally, intravenously, etc.) to a subject (e.g., in a clinical setting)such as medicinal compositions. For example, the composition may be inthe form of an intravenous fluid (e.g., saline, Ringer's lactate). Insome cases, the hydrogen and/or noble gas(es) may be added tocompositions such as nasal sprays, ear drops, eye drops, toothpastes,mouthwashes, and/or topical compositions.

In some embodiments, the composition may be configured to beadministered to a subject topically (e.g., a topical composition).Non-limiting examples of topical compositions include topical solutions,cosmetics, creams (e.g., steroidal creams, antibiotic creams), foams,pastes, gels, lotions, soaps, jellies (e.g., petroleum jelly), lipbalms, shampoos, and ointments.

In certain embodiments, hydrogen gas and/or noble gas(es) may be addedto a compositions comprising a physiological composition such as blood,plasma, sputum, mucus, urine, and/or sweat. In some embodiments, thephysiological composition may be administered to a subject (e.g.,hydrogen gas and/or noble gas(es) may be added to a physiologicalcomposition such as blood and administered to the subject).Advantageously, the addition of hydrogen gas and/or noble gas(es) toblood may, for example, aid in the production and/or preservation of theblood.

In some embodiments, one or more additives may be present in thecomposition. Non-limiting examples of additives include sugar,electrolytes, caffeine, salt(s), flavoring, vitamins, herbs, aminoacids, tea extracts, seed extracts, fruit extracts, and combinationsthereof. The one or more additives may be present in any suitableamount. For example, in some embodiments, the additive is present in thecomposition in an amount of greater than or equal to 0.1 vol %, greaterthan or equal to 0.2 vol %, greater than or equal to 0.25 vol %, greaterthan or equal to 0.5 vol %, greater than or equal to 0.75 vol %, greaterthan or equal to 1 vol %, greater than or equal to 1.25 vol %, greaterthan or equal to 1.5 vol %, greater than or equal to 1.75 vol %, greaterthan or equal to 2 vol %, greater than or equal to 2.25 vol %, greaterthan or equal to 2.5 vol %, greater than or equal to 3 vol %, greaterthan or equal to 3.5 vol %, greater than or equal to 4 vol %, or greaterthan or equal to 4.5 vol % versus the total volume of the composition.

In certain embodiments, the additive is present in the composition in anamount less than or equal to 5 vol %, less than or equal to 4.5 vol %,less than or equal to 4 vol %, less than or equal to 3.5 vol %, lessthan or equal to 3 vol %, less than or equal to 2.5 vol %, less than orequal to 2.25 vol %, less than or equal to 2 vol %, less than or equalto 1.75 vol %, less than or equal to 1.5 vol %, less than or equal to1.25 vol %, less than or equal to 1 vol %, less than or equal to 0.75vol %, less than or equal to 0.5 vol %, less than or equal to 0.25 vol%, or less than or equal to 0.2 vol % versus the total volume of thecomposition. Combinations of the above-referenced ranges are alsopossible (e.g., greater than or equal to 0.1 vol % and less than orequal to 5 vol %). Other ranges are also possible.

In some embodiments, a composition comprises hydrogen gas, a noble gas(e.g., xenon gas), and one or more additives, in the ranges listed abovewith the remainder of the composition being an ingestible composition, aphysiological composition, and/or a topical composition.

In certain embodiments, an ingestible composition is present in anamount of greater than or equal to 90 wt %, greater than or equal to 91wt %, greater than or equal to 92 wt %, greater than or equal to 93 wt%, greater than or equal to 94 wt %, greater than or equal to 95 wt %,greater than or equal to 96 wt %, greater than or equal to 97 wt %,greater than or equal to 98 wt %, greater than or equal to 99 wt %,greater than or equal to 99.5 wt %, or greater than or equal to 99.9 wt% versus the total composition weight. In some embodiments, theingestible composition is present in an amount of less than or equal to99.99 wt %, less than or equal to 99.9 wt %, less than or equal to 99.5wt %, less than or equal to 99 wt %, less than or equal to 98 wt %, lessthan or equal to 97 wt %, less than or equal to 96 wt %, less than orequal to 95 wt %, less than or equal to 94 wt %, less than or equal to93 wt %, less than or equal to 92 wt %, or less than or equal to 91 wt %water versus the total composition weight. Combinations of theabove-referenced ranges are also possible (e.g., greater than or equalto 90 wt % and less than or equal to 99.99 wt %, greater than or equalto 95 wt % and less than or equal to 99.99 wt %, greater than or equalto 98 wt % and less than or equal to 99.99 wt %). Other ranges are alsopossible.

In certain embodiments, ingestible composition is present in an amountof greater than or equal to 90 vol %, greater than or equal to 91 vol %,greater than or equal to 92 vol %, greater than or equal to 93 vol %,greater than or equal to 94 vol %, greater than or equal to 95 vol %,greater than or equal to 96 vol %, greater than or equal to 97 vol %,greater than or equal to 98 vol %, greater than or equal to 99 vol %,greater than or equal to 99.5 vol %, or greater than or equal to 99.9vol % versus the total volume of the composition. In some embodiments,the ingestible composition is present in an amount of less than or equalto 99.99 vol %, less than or equal to 99.9 vol %, less than or equal to99.5 vol %, less than or equal to 99 vol %, less than or equal to 98 vol%, less than or equal to 97 vol %, less than or equal to 96 vol %, lessthan or equal to 95 vol %, less than or equal to 94 vol %, less than orequal to 93 vol %, less than or equal to 92 vol %, or less than or equalto 91 vol % versus the total volume of the composition. Combinations ofthe above-referenced ranges are also possible (e.g., greater than orequal to 90 vol % and less than or equal to 99.99 vol %, greater than orequal to 95 vol % and less than or equal to 99.99 vol %, greater than orequal to 98 vol % and less than or equal to 99.99 vol %). Other rangesare also possible.

In certain embodiments, a physiological composition is present in anamount of greater than or equal to 90 wt %, greater than or equal to 91wt %, greater than or equal to 92 wt %, greater than or equal to 93 wt%, greater than or equal to 94 wt %, greater than or equal to 95 wt %,greater than or equal to 96 wt %, greater than or equal to 97 wt %,greater than or equal to 98 wt %, greater than or equal to 99 wt %,greater than or equal to 99.5 wt %, or greater than or equal to 99.9 wt% versus the total composition weight. In some embodiments, thephysiological composition is present in an amount of less than or equalto 99.99 wt %, less than or equal to 99.9 wt %, less than or equal to99.5 wt %, less than or equal to 99 wt %, less than or equal to 98 wt %,less than or equal to 97 wt %, less than or equal to 96 wt %, less thanor equal to 95 wt %, less than or equal to 94 wt %, less than or equalto 93 wt %, less than or equal to 92 wt %, or less than or equal to 91wt % water versus the total composition weight. Combinations of theabove-referenced ranges are also possible (e.g., greater than or equalto 90 wt % and less than or equal to 99.99 wt %, greater than or equalto 95 wt % and less than or equal to 99.99 wt %, greater than or equalto 98 wt % and less than or equal to 99.99 wt %). Other ranges are alsopossible.

In certain embodiments, the physiological composition is present in anamount of greater than or equal to 90 vol %, greater than or equal to 91vol %, greater than or equal to 92 vol %, greater than or equal to 93vol %, greater than or equal to 94 vol %, greater than or equal to 95vol %, greater than or equal to 96 vol %, greater than or equal to 97vol %, greater than or equal to 98 vol %, greater than or equal to 99vol %, greater than or equal to 99.5 vol %, or greater than or equal to99.9 vol % versus the total volume of the composition. In someembodiments, the physiological composition is present in an amount ofless than or equal to 99.99 vol %, less than or equal to 99.9 vol %,less than or equal to 99.5 vol %, less than or equal to 99 vol %, lessthan or equal to 98 vol %, less than or equal to 97 vol %, less than orequal to 96 vol %, less than or equal to 95 vol %, less than or equal to94 vol %, less than or equal to 93 vol %, less than or equal to 92 vol%, or less than or equal to 91 vol % versus the total volume of thecomposition. Combinations of the above-referenced ranges are alsopossible (e.g., greater than or equal to 90 vol % and less than or equalto 99.99 vol %, greater than or equal to 95 vol % and less than or equalto 99.99 vol %, greater than or equal to 98 vol % and less than or equalto 99.99 vol %). Other ranges are also possible.

In certain embodiments, a topical composition is present in an amount ofgreater than or equal to 90 wt %, greater than or equal to 91 wt %,greater than or equal to 92 wt %, greater than or equal to 93 wt %,greater than or equal to 94 wt %, greater than or equal to 95 wt %,greater than or equal to 96 wt %, greater than or equal to 97 wt %,greater than or equal to 98 wt %, greater than or equal to 99 wt %,greater than or equal to 99.5 wt %, or greater than or equal to 99.9 wt% versus the total composition weight. In some embodiments, the topicalcomposition is present in an amount of less than or equal to 99.99 wt %,less than or equal to 99.9 wt %, less than or equal to 99.5 wt %, lessthan or equal to 99 wt %, less than or equal to 98 wt %, less than orequal to 97 wt %, less than or equal to 96 wt %, less than or equal to95 wt %, less than or equal to 94 wt %, less than or equal to 93 wt %,less than or equal to 92 wt %, or less than or equal to 91 wt % waterversus the total composition weight. Combinations of theabove-referenced ranges are also possible (e.g., greater than or equalto 90 wt % and less than or equal to 99.99 wt %, greater than or equalto 95 wt % and less than or equal to 99.99 wt %, greater than or equalto 98 wt % and less than or equal to 99.99 wt %). Other ranges are alsopossible.

In certain embodiments, the topical composition is present in an amountof greater than or equal to 90 vol %, greater than or equal to 91 vol %,greater than or equal to 92 vol %, greater than or equal to 93 vol %,greater than or equal to 94 vol %, greater than or equal to 95 vol %,greater than or equal to 96 vol %, greater than or equal to 97 vol %,greater than or equal to 98 vol %, greater than or equal to 99 vol %,greater than or equal to 99.5 vol %, or greater than or equal to 99.9vol % versus the total volume of the composition. In some embodiments,the topical composition is present in an amount of less than or equal to99.99 vol %, less than or equal to 99.9 vol %, less than or equal to99.5 vol %, less than or equal to 99 vol %, less than or equal to 98 vol%, less than or equal to 97 vol %, less than or equal to 96 vol %, lessthan or equal to 95 vol %, less than or equal to 94 vol %, less than orequal to 93 vol %, less than or equal to 92 vol %, or less than or equalto 91 vol % versus the total volume of the composition. Combinations ofthe above-referenced ranges are also possible (e.g., greater than orequal to 90 vol % and less than or equal to 99.99 vol %, greater than orequal to 95 vol % and less than or equal to 99.99 vol %, greater than orequal to 98 vol % and less than or equal to 99.99 vol %). Other rangesare also possible.

As mentioned, the composition may be any of a variety of drinkableliquids in various embodiments, such as water, a fruit juice, coffee,tea, a sports drink, an energy drink, soda pop, milk, an alcoholicdrink, etc. In some cases, the composition may be in the form ofadministrable to a subject (e.g., in an intravenous bag or pouch forintravenous delivery such as comprising saline).

In an exemplary embodiment, the article (e.g., the container) isconfigured for intravenous delivery of the composition contained thereinto a subject and comprises saline (e.g., NaCl dissolved in water). Insome such embodiments, the additive is NaCl. In some cases, thecomposition may be normal saline (i.e. 0.9 wt %/vol % NaCl per totalvolume of the water present in the composition) and comprises hydrogengas and xenon gas. In some embodiments, NaCl is present in thecomposition in an amount of greater than or equal to 0.1 wt %, greaterthan or equal to 0.2 wt %, greater than or equal to 0.3 wt %, greaterthan or equal to 0.5 wt %, greater than or equal to 0.7 wt %, greaterthan or equal to 0.9 wt %, greater than or equal to 1 wt %, greater thanor equal to 1.2 wt %, greater than or equal to 1.5 wt %, greater than orequal to 1.7 wt %, or greater than or equal to 2 wt % per total volumeof the water present in the composition). In certain embodiments, NaClis present in the composition in an amount of less than or equal to 2.5wt %, less than or equal to 2 wt %, less than or equal to 1.7 wt %, lessthan or equal to 1.5 wt %, less than or equal to 1.2 wt %, less than orequal to 1 wt %, less than or equal to 0.9 wt %, less than or equal to0.7 wt %, less than or equal to 0.5 wt %, less than or equal to 0.3 wt%, or less than or equal to 0.2 wt %. Combinations of theabove-referenced ranges are also possible (e.g., greater than or equalto 0.1 wt % and less than or equal to 2.5 wt %, greater than or equal to0.7 wt % and less than or equal to 1 wt %). Other ranges are alsopossible.

In some embodiments, the composition comprises hydrogen gas, a noble gas(e.g., xenon gas), and one or more additives, in the ranges listed abovewith the remainder of the composition being water. In certainembodiments, water is present in the liquid in an amount of greater thanor equal to 90 wt %, greater than or equal to 91 wt %, greater than orequal to 92 wt %, greater than or equal to 93 wt %, greater than orequal to 94 wt %, greater than or equal to 95 wt %, greater than orequal to 96 wt %, greater than or equal to 97 wt %, greater than orequal to 98 wt %, greater than or equal to 99 wt %, greater than orequal to 99.5 wt %, or greater than or equal to 99.9 wt % versus thetotal liquid weight. In some embodiments, the liquid comprises less thanor equal to 99.99 wt %, less than or equal to 99.9 wt %, less than orequal to 99.5 wt %, less than or equal to 99 wt %, less than or equal to98 wt %, less than or equal to 97 wt %, less than or equal to 96 wt %,less than or equal to 95 wt %, less than or equal to 94 wt %, less thanor equal to 93 wt %, less than or equal to 92 wt %, or less than orequal to 91 wt % water versus the total liquid weight. Combinations ofthe above-referenced ranges are also possible (e.g., greater than orequal to 90 wt % and less than or equal to 99.99 wt %, greater than orequal to 95 wt % and less than or equal to 99.99 wt %, greater than orequal to 98 wt % and less than or equal to 99.99 wt %). Other ranges arealso possible.

In certain embodiments, water is present in the composition in an amountof greater than or equal to 90 vol %, greater than or equal to 91 vol %,greater than or equal to 92 vol %, greater than or equal to 93 vol %,greater than or equal to 94 vol %, greater than or equal to 95 vol %,greater than or equal to 96 vol %, greater than or equal to 97 vol %,greater than or equal to 98 vol %, greater than or equal to 99 vol %,greater than or equal to 99.5 vol %, or greater than or equal to 99.9vol % versus the total volume of the liquid. In some embodiments, theliquid comprises less than or equal to 99.99 vol %, less than or equalto 99.9 vol %, less than or equal to 99.5 vol %, less than or equal to99 vol %, less than or equal to 98 vol %, less than or equal to 97 vol%, less than or equal to 96 vol %, less than or equal to 95 vol %, lessthan or equal to 94 vol %, less than or equal to 93 vol %, less than orequal to 92 vol %, or less than or equal to 91 vol % versus the totalvolume of the liquid. Combinations of the above-referenced ranges arealso possible (e.g., greater than or equal to 90 vol % and less than orequal to 99.99 vol %, greater than or equal to 95 vol % and less than orequal to 99.99 vol %, greater than or equal to 98 vol % and less than orequal to 99.99 vol %). Other ranges are also possible.

In some embodiments, the composition may be used to improve the healthof a subject. For example, the composition may reduce oxidative stressand/or reduce muscle fatigue (e.g., after exercise and/or athleticactivity). In certain embodiments, the composition may improve asubject's overall well-being including, for example, a feeling ofincreased energy levels, hastened recovery after exercise, improvedmemory, increased strength, and/or reduced tiredness. In some cases, thecomposition may be particularly delectable to the subject. In addition,in some cases, the composition may be used to treat a disease, disorder,or other clinically recognized condition, or for prophylactic purposes,or for providing physiological benefits, and has a clinicallysignificant effect on the body of the subject to treat and/or preventthe disease, disorder, or condition, and/or has a clinically significanteffect on the subject's physiology. In other embodiments, thecomposition may provide performance enhancement to a subject while, forexample, exercising and/or performing athletic activities.

In some cases, the composition may be administered to a subject (e.g.,administered to a subject to treat a disease, disorder, or otherclinically recognized condition, or for prophylactic purposes). Incertain embodiments, the article may be administered orally,intravenously, rectally, nasally (e.g., via a nasal spray, via a nasaldropper), or uretherally (e.g., via a catheter). In certain embodiments,the composition may be orally administered to a subject, (e.g., ingestedor drunk by a subject, encapsulated in a pill (e.g., the composition iscontained in a capsule such as a gel-capsule)). In certain embodiments,the composition may be consumed orally (e.g., eaten, drunk, swallowed).

In such embodiments in which the composition is administered to asubject, the composition may comprise hydrogen gas in an amount ofgreater than or equal to greater than or equal to 0.1 ppm and less thanor equal to 5 ppm and xenon gas (and/or other noble gases) in an amountof greater than or equal to 1 ppm and less than or equal to 20 ppm.

In some embodiments, the composition may be administered intravenously.In some such embodiments, the composition comprises hydrogen gas in anamount of greater than or equal to greater than or equal to 0.1 ppm andless than or equal to 5 ppm and xenon gas (and/or other noble gases) inan amount of greater than or equal to 1 ppm and less than or equal to 20ppm.

Without wishing to be bound by any theory, while xenon and other noblegases may not be directly involved in any chemical reactions, such gasesmay participate in physical interactions within a subject (for example,by blocking receptors, creating size exclusion effects, and/or bycompeting with proteins), thereby resulting in various biologicaleffects. This may be useful, for example, for the treatment of animaland human diseases, for improvement in athletic performance, for theenhancement of the overall health of a subject, or the like.

For example, in one set of embodiments, xenon may be used to inducecardioprotection and/or neuroprotection through a variety of mechanisms.In certain cases, a composition as described herein can be used to treatconditions such as ischemia, e.g., partial ischemia or restriction inblood supply to tissues. For instance, a composition may be administeredto a subject, e.g., on a regular basis as discussed herein, to protectneural and/or cardiac function. Without wishing to be bound by anytheory, it is believed that xenon may affect Ca²⁺, K⁺, KATP\HIF, and/orNMDA antagonism; xenon may also activate PKC-epsilon, p38-MAPK,ATP-sensitive potassium channel, and/or hypoxia inducible factor 1 alpha(HIF1a), thereby allowing cardioprotective and/or neuroprotectiveeffects to occur.

In another set of embodiments, xenon may be used to increase productionof erythropoietin. This may be useful, for example, to increase redblood cells, e.g., to treat anemic subjects, or improve athleticperformance. Without wishing to be bound by any theory, it is believedthat xenon may enhance production of HIF1a, which is a transcriptionfactor able to respond to hypoxic conditions. Accordingly, in someembodiments, a composition as described herein can be used to treatanemia or other conditions in a subject. In another set of embodiments,a composition as described herein may be used to increase a subject'sphysical energy levels, e.g., for improvement in athletic performance.

In addition, in low doses, xenon may cause certain analgesic effects,which may facilitate improved athletic performance in some cases (e.g.,due to lower or reduced pain). For example, xenon may inhibit nicotinicacetylcholine alpha-4-beta-2 (α₄β₂) receptors, plasma membraneCa²⁺ATPase, and/or the serotonin 5-HT3 receptor. Xenon may also be anantagonist of high-affinity glycine-site NMDA, or it may activate thetwo-pore domain potassium channel TREK-1.

In some cases, xenon and other and other noble gases may exhibitsynergistic effects with hydrogen (H₂), e.g., for certain applicationssuch as for the treatment of animal and human diseases, for improvementin athletic performance, for the enhancement of the overall health of asubject, or the like.

Hydrogen may act within the body as an antioxidant. In some cases,hydrogen may be used to treat various oxidative stress conditions, forexample, as an antioxidant, or by interaction with proteins such asNRF2. For example, strenuous exercise may cause oxidative stresses,e.g., due to muscle fatigue. Hydrogen may accordingly be used in someembodiments to treat athletes and improve athletic performance. Thus, insome cases, compositions such as those discussed herein, e.g.,containing hydrogen and/or xenon (and/or other noble gases) may beprovided to a subject to enhance athletic performance.

In addition, in some cases, hydrogen may be used to treat oxidativestress diseases and conditions such as smoking, exposure to ultravioletrays, air pollution, aging, physical or psychological stress, cancer, orthe aging process. Xenon (and/or other noble gases) may facilitatetreatment by increasing red blood cell levels, e.g., as discussedherein. In addition, hydrogen may also exhibit other effects, such asanti-inflammatory properties, that may be useful in conjunction withxenon and/or other noble gases.

In certain embodiments of the invention, the administration of variouscompositions of the invention may be designed so as to result insequential exposures to the composition over a certain time period, forexample, hours, days, weeks, months, or years. This may be accomplished,for example, by repeated administrations of a composition of theinvention by one or more of the methods described herein. In some cases,compositions may be applied to the subject on a relatively regular orperiodic basis; e.g., a subject may drink a container each day, or atwo, three, four, or more containers a day, or a container every otherday, every third day, every fourth day, etc. Somewhat more irregularschedules are also possible (e.g., a regular number of containers perweek or per month, etc.).

Thus, the compositions of the present invention may be administered inmultiple doses over extended period of time. For any compositiondescribed herein the therapeutically effective amount can be initiallydetermined from animal models. The applied dose can be adjusted based onthe relative bioavailability and potency of the administeredcomposition. Adjusting the dose to achieve maximal efficacy based on themethods described above and other methods as are well-known in the artis well within the capabilities of the ordinarily skilled artisan.

When administered to a subject, effective amounts will depend on theparticular condition being treated and the desired outcome. Atherapeutically effective dose may be determined by those of ordinaryskill in the art, for instance, employing factors such as thosedescribed herein and using no more than routine experimentation.

In administering the compositions of the invention to a subject, dosingamounts, dosing schedules, routes of administration, and the like may beselected so as to affect known activities of these compositions. Dosagesmay be estimated based on the results of experimental models, optionallyin combination with the results of assays of compositions of the presentinvention. Dosage may be adjusted appropriately to achieve desired druglevels, local or systemic, depending upon the mode of administration.The doses may be given in one or several administrations per day.Multiple doses per day are also contemplated in some cases to achieveappropriate systemic levels of the composition within the subject orwithin the active site of the subject.

The dosage may be given in some cases at the maximum amount whileavoiding or minimizing any potentially detrimental side effects withinthe subject. The dosage of the composition that is actually administeredis dependent upon factors such as the final concentration desired at theactive site, the method of administration to the subject, the efficacyof the composition, the longevity of the composition within the subject,the timing of administration, the effect of concurrent treatments (e.g.,as in a cocktail), etc. The dose delivered may also depend on conditionsassociated with the subject, and can vary from subject to subject insome cases. For example, the age, sex, weight, size, environment,physical conditions, or current state of health of the subject may alsoinfluence the dose required and/or the concentration of the composition.Variations in dosing may occur between different individuals or evenwithin the same individual on different days. It may be preferred that amaximum dose be used, that is, the highest safe dose according to soundmedical judgment. Preferably, the dosage form is such that it does notsubstantially deleteriously affect the subject.

Administration of the composition can be alone, or in combination withother therapeutic agents and/or compositions. In certain embodiments ofthe invention, a composition can be combined with a suitablepharmaceutically acceptable carrier, for example, within a suitableliquid. In general, pharmaceutically acceptable carriers suitable foruse in the invention are well-known to those of ordinary skill in theart. As used herein, a “pharmaceutically acceptable carrier” refers to anon-toxic material that does not significantly interfere with theeffectiveness of the biological activity of the active composition(s) tobe administered, but is used as a formulation ingredient, for example,to stabilize or protect the active composition(s) within the compositionbefore use. The carrier may include one or more compatible solid orliquid fillers, diluents or encapsulating substances which are suitablefor administration to a human or other vertebrate animal. The term“carrier” denotes an organic or inorganic ingredient, which may benatural or synthetic, with which one or more compositions of theinvention are combined to facilitate the application of the composition.The carrier may be co-mingled or otherwise mixed with one or morecompositions of the present invention, and with each other, in a mannersuch that there is no interaction which would substantially impair thedesired pharmaceutical efficacy. Those skilled in the art will know ofsuitable carriers, such as saline, or will be able to ascertain such,using only routine experimentation.

The formulations of the invention are administered in pharmaceuticallyacceptable solutions, which may routinely contain pharmaceuticallyacceptable concentrations of salt, buffering agents, preservatives,compatible carriers, adjuvants, emulsifiers, diluents, excipients,chelating agents, fillers, drying agents, antioxidants, antimicrobials,preservatives, binding agents, bulking agents, silicas, solubilizers,stabilizers and optionally other therapeutic ingredients, that may beused with the active composition. For example, if the formulation is aliquid, the carrier may be a solvent, partial solvent, or non-solvent,and may be aqueous or organically based. Examples of suitableformulation ingredients include diluents such as calcium carbonate,sodium carbonate, lactose, kaolin, calcium phosphate, or sodiumphosphate; granulating and disintegrating agents such as corn starch oralgenic acid; binding agents such as starch, gelatin or acacia;lubricating agents such as magnesium stearate, stearic acid, or talc;time-delay materials such as glycerol monostearate or glyceroldistearate; suspending agents such as sodium carboxymethylcellulose,methylcellulose, hydroxypropylmethylcellulose, sodium alginate,polyvinylpyrrolidone; dispersing or wetting agents such as lecithin orother naturally-occurring phosphatides; thickening agents such as cetylalcohol or beeswax; buffering agents such as acetic acid and saltsthereof, citric acid and salts thereof, boric acid and salts thereof, orphosphoric acid and salts thereof; or preservatives such as benzalkoniumchloride, chlorobutanol, parabens, or thimerosal. Suitable carrierconcentrations can be determined by those of ordinary skill in the art,using no more than routine experimentation. The compositions of theinvention may be formulated into preparations in solid, semi-solid,liquid or gaseous forms such as tablets, capsules, elixirs, powders,granules, ointments, solutions, depositories, inhalants or injectables.Those of ordinary skill in the art will know of other suitableformulation ingredients, or will be able to ascertain such, using onlyroutine experimentation.

Suitable buffering agents include: acetic acid and a salt (1-2% w/v);citric acid and a salt (1-3% w/v); boric acid and a salt (0.5-2.5% w/v);and phosphoric acid and a salt (0.8-2% w/v). Suitable preservativesinclude benzalkonium chloride (0.003-0.03% w/v); chlorobutanol (0.3-0.9%w/v); parabens (0.01-0.25% w/v) and thimerosal (0.004-0.02% w/v).

Preparations include sterile aqueous or non-aqueous solutions,suspensions and emulsions, which can be isotonic with the blood of thesubject in certain embodiments. Examples of non-aqueous solvents arepolypropylene glycol, polyethylene glycol, vegetable oil such as oliveoil, sesame oil, coconut oil, arachis oil, peanut oil, mineral oil,injectable organic esters such as ethyl oleate, or fixed oils includingsynthetic mono or di-glycerides. Aqueous carriers include water,alcoholic/compositions, emulsions or suspensions, including saline andbuffered media. Parenteral vehicles include sodium chloride solution,1,3-butandiol, Ringer's dextrose, dextrose and sodium chloride, lactatedRinger's or fixed oils. Intravenous vehicles include fluid and nutrientreplenishers, electrolyte replenishers (such as those based on Ringer'sdextrose), and the like. Preservatives and other additives may also bepresent such as, for example, antimicrobials, antioxidants, chelatingagents and inert gases and the like. Those of skill in the art canreadily determine the various parameters for preparing and formulatingthe compositions of the invention without resort to undueexperimentation.

The present invention also provides any of the above-mentionedcompositions in kits, optionally including instructions for use of thecomposition for the treatment of a condition discussed herein. That is,the kit can include a description of use of the composition forparticipation in any biological or chemical mechanism disclosed hereinassociated with a condition discussed herein. The kit can include adescription of use of the compositions as discussed herein. The kit alsocan include instructions for use of a combination of two or morecompositions of the invention, or instruction for use of a combinationof a composition of the invention and one or more other compositions.Instructions also may be provided for administering the composition byany suitable technique as previously described, for example, orally,intravenously, pump or implantable delivery device, or via another knownroute of drug delivery.

The kits described herein may also contain one or more containers, whichmay contain the composition and other ingredients as previouslydescribed. The kits also may contain instructions for mixing, diluting,and/or administrating the compositions of the invention in some cases.The kits also can include other containers with one or more solvents,surfactants, preservative and/or diluents (e.g., normal saline (0.9%NaCl), or 5% dextrose) as well as containers for mixing, diluting oradministering the components in a sample or to a subject in need of suchtreatment.

The compositions of the kit may be provided as any suitable form, forexample, as liquid solutions. In embodiments where liquid forms of thecomposition are used, the liquid form may be concentrated or ready touse. The solvent will depend on the composition and the mode of use oradministration. Suitable solvents for drug compositions are well known,for example as previously described, and are available in theliterature. The solvent will depend on the composition and the mode ofuse or administration.

In certain embodiments, the articles, compositions, and compositionsdescribed herein are substantially non-toxic. The term “non-toxic”refers to a substance that does not comprise a toxic compound. The term“toxic” refers to a substance showing detrimental, deleterious, harmful,or otherwise negative effects on a subject, tissue, or cell when orafter administering the substance to the subject or contacting thetissue or cell with the substance, compared to the subject, tissue, orcell prior to administering the substance to the subject or contactingthe tissue or cell with the substance. In certain embodiments, theeffect is death or destruction of the subject, tissue, or cell. Incertain embodiments, the effect is a detrimental effect on themetabolism of the subject, tissue, or cell. In certain embodiments, atoxic substance is a substance that has a median lethal dose (LD50) ofnot more than 500 milligrams per kilogram of body weight whenadministered orally to an albino rat weighing between 200 and 300 grams,inclusive. In certain embodiments, a toxic substance is a substance thathas an LD50 of not more than 1,000 milligrams per kilogram of bodyweight when administered by continuous contact for 24 hours (or less ifdeath occurs within 24 hours) with the bare skin of an albino rabbitweighing between two and three kilograms, inclusive. In certainembodiments, a toxic substance is a substance that has an LC50 in air ofnot more than 2,000 parts per million by volume of gas or vapor, or notmore than 20 milligrams per liter of mist, fume, or dust, whenadministered by continuous inhalation for one hour (or less if deathoccurs within one hour) to an albino rat weighing between 200 and 300grams, inclusive.

A “subject” refers to any animal such as a mammal (e.g., a human).Non-limiting examples of subjects include a human, a non-human primate,a cow, a horse, a pig, a sheep, a goat, a dog, a cat or a rodent such asa mouse, a rat, a hamster, a bird, a fish, or a guinea pig. Generally,the invention is directed toward use with humans. In some embodiments, asubject may demonstrate health benefits, e.g., upon administration ofthe liquid.

As used herein, a “fluid” is given its ordinary meaning, i.e., a liquidor a gas. A fluid cannot maintain a defined shape and will flow duringan observable time frame to fill the container in which it is put. Thus,the fluid may have any suitable viscosity that permits flow. If two ormore fluids are present, each fluid may be independently selected amongessentially any fluids (liquids, gases, and the like) by those ofordinary skill in the art.

A co-owned U.S. patent application filed on Aug. 8, 2017, entitled“Medication Enhancement Using Hydrogen,” by Nicholas Perricone isincorporated herein by reference in its entirety for all purposes.

EXAMPLES

The following examples illustrate embodiments of certain aspects of theinvention. It should be understood that the methods and/or materialsdescribed herein may be modified and/or scaled, as known to those ofordinary skill in the art.

Prophetic Example 1

A container containing a composition is provided. A system comprising avalve configured and designed for the flow of liquid hydrogen is placedinto fluidic communication with the container. Liquid hydrogen is flowedthrough the system such that greater than or equal to 0.1 mg and lessthan or equal to 5 mg of liquid hydrogen is introduced to one liter ofthe composition and the container is sealed. The liquid hydrogen in thesealed container changes phase into gaseous hydrogen, such that thecontainer is pressurized and such that the gaseous hydrogen is presentin the composition in an amount of greater than or equal to 0.1 ppm andless than or equal to 5 ppm.

Prophetic Example 2

A container containing a composition comprising an ingestiblecomposition such as a drink and/or food is provided. A system comprisinga valve configured and designed for the flow of liquid hydrogen isplaced into fluidic communication with the container. Liquid hydrogen isflowed through the system such that greater than or equal to 0.1 mg andless than or equal to 5 mg of liquid hydrogen is introduced to one literof the ingestible composition and the container is sealed.

Liquid hydrogen and/or liquid nitrogen may be used to freeze at least aportion of the ingestible composition. In one exemplary case, cream andsugar may be mixed together and at least partially frozen using liquidhydrogen and/or liquid nitrogen, such that liquid hydrogen is providedto the composition in an amount of greater than or equal to 0.1 mg andless than or equal to 5 mg per liter of the composition.

While several embodiments of the present invention have been describedand illustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and/or structures for performing thefunctions and/or obtaining the results and/or one or more of theadvantages described herein, and each of such variations and/ormodifications is deemed to be within the scope of the present invention.More generally, those skilled in the art will readily appreciate thatall parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the teachings of thepresent invention is/are used. Those skilled in the art will recognize,or be able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described and claimed. Thepresent invention is directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe scope of the present invention.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Other elements may optionallybe present other than the elements specifically identified by the“and/or” clause, whether related or unrelated to those elementsspecifically identified unless clearly indicated to the contrary. Thus,as a non-limiting example, a reference to “A and/or B,” when used inconjunction with open-ended language such as “comprising” can refer, inone embodiment, to A without B (optionally including elements other thanB); in another embodiment, to B without A (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” and the like are to be understoodto be open-ended, i.e., to mean including but not limited to. Only thetransitional phrases “consisting of” and “consisting essentially of”shall be closed or semi-closed transitional phrases, respectively, asset forth in the United States Patent Office Manual of Patent ExaminingProcedures, Section 2111.03.

1-69. (canceled)
 70. An article, comprising: a sealed containercontaining a composition pressurized using liquid hydrogen.
 71. Anarticle as in claim 70, wherein the sealed container further comprisesgreater than or equal to 0.1 mg of a liquid noble gas.
 72. An article asin claim 70, wherein the sealed container is a can, bottle, jar, pouch,box, bag, or capsule.
 73. An article as in claim 70, wherein the sealedcontainer contains a pressure at least 1 psi greater than atmosphericpressure.
 74. An article as in claim 70, wherein the composition is adrinkable liquid.
 75. A method, comprising: introducing, into acontainer comprising a composition, greater than or equal to 0.1 mg ofliquid hydrogen; and sealing the container.
 76. A method as in claim 75,wherein the liquid hydrogen changes phase to gaseous hydrogen aftersealing the container such that the contents within the container arepressurized.
 77. A method as in claim 75, wherein introducing the liquidhydrogen comprises dispensing the liquid hydrogen into the container viaa dispenser.
 78. A method as in claim 77, wherein the dispenser isconfigured and arranged introduce liquid hydrogen into a plurality ofcontainers at a rate of greater than or equal to 100 containers perminute.
 79. A method as in claim 77, wherein the disperser comprises avalve for introducing liquid hydrogen into the composition, and thevalve is configured such that the liquid hydrogen does not substantiallychange phase while flowing through the valve.
 80. A method as in claim75, wherein the composition is a drinkable liquid.
 81. A method as inclaim 75, further comprising introducing an inert gas proximate thecontainer.
 82. A method as in claim 75, further comprising introducing,into the container, greater than or equal to 0.1 mg of liquid noble gas.83. A system, comprising: a source comprising liquid hydrogen; and adispenser in fluid communication with the source, the dispenserconfigured and arranged to introduce greater than or equal to 0.1 mg ofliquid hydrogen into containers associated with the dispenser at a rateof 100 containers per minute.
 84. A system as in claim 83, wherein thedispenser comprises a value, wherein the valve is configured anddesigned for the introduction of liquid hydrogen into the container. 85.A system as in claim 83, wherein the composition is a drinkable liquid.86. A system as in claim 83, further comprising a container sealingsystem configured and designed to seal the containers after thedispenser has dispensed liquid hydrogen into the containers.
 87. Asystem as in claim 83, wherein the source further comprises a liquidnoble gas.
 88. A system as in claim 83, wherein the system furthercomprises a gaseous hydrogen removal system in gaseous communicationwith the dispenser.
 89. A system as in claim 88, wherein the gaseoushydrogen removal system comprises a fan.